title: Triazole antifungals. II. Synthesis and antifungal activities of 3-acyl-4-methyloxazolidine derivatives.
abstract: Triazole compounds with an oxazolidine ring were designed and synthesized as a potential inhibitor of the fungal cytochrome P450 14 alpha-demethylase. In testing for antifungal activity against a mouse systemic Candida albicans infection, (4R,5R)-3-acyl-4-methyloxazolidine derivatives 4 exhibited remarkably high efficacy after oral or parenteral dosing. The potent activity of 4 is hypothesized to be a consequence of a structural similarity between 4 and lanosterol, a target molecule of the cytochrome P450 14 alpha-demethylase. Highly stereoselective synthesis of these oxazolidines is also described.
authors.affiliation: Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Konosu
authors.forename: Y
authors.initials: Y
authors.lastname: Tajima
authors.forename: N
authors.initials: N
authors.lastname: Takeda
authors.forename: T
authors.initials: T
authors.lastname: Miyaoka
authors.forename: M
authors.initials: M
authors.lastname: Kasahara
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: S
authors.initials: S
authors.lastname: Oida
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000138:chemical synthesis / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D010080:Oxazoles; D014230:Triazoles